This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary progressive aphasia (PPA) is a communicative disorder caused by the loss or dysfunction of neurons within language-related areas of the brain. Although patients initially present with isolated language dysfunction, the disorder is progressive and leads eventually to a non-communicative state. In contrast to cerebrovascular accidents where the onset of symptoms is abrupt, where the lesion is almost never confined just to the language network, and where all neural elements within the lesioned site are destroyed indiscriminately, PPA leads to a partial and progressive dysfunction and eventual loss of specific neuronal populations within affected areas. The resultant clinical picture is characterized by symptom combinations and dissociations rarely seen in other forms of aphasia. Previous studies from our group and others have demonstrated the regional involutional changes in PPA. However, course of these changes, their spread to nearby cortical regions, and the correspondence with functional and metabolic changes has not been examined over time. The primary aims of this component of the program project grant are to examine these issues: Changes in gray and white matter with PPA will be tracked over time using high resolution magnetic resonance imaging and high-dimensional spatiotemporal mapping. This will be performed in collaboration with the Laboratory of Neuro Imaging at UCLA. The association of these changes with alterations in lexical processing will be examined using functional magnetic resonance imaging. Finally, the correspondence between anatomic and metabolic changes will be investigated by combining MRI images with fluorodeoxyglucose Positron Emission Tomography.